Reducing uncomfortable side effects of abdominal distension in patients treated in hydrocolonic preparation units

ABSTRACT

Systems and methods are provided to limit abdominal distension and alleviate uncomfortable side effects related to it—in patients treated in hydrocolonic preparation units. Systems may comprise a water delivery unit comprising a controllable water supply, configured to introduce water controllably into the patient&#39;s large intestine, a drainage configured to drain, by gravity, the introduced water with contents of the patient&#39;s large intestine and a controller. The drainage comprises a drainage pipe and sensor(s) such as camera(s) configured to continuously measure the amount of drained water drained by the drainage pipe. The controller is configured to control the water introduction with respect to the measured amount of drained water, keeping an amount of water retained in the patient below a specified water retention threshold to reduce uncomfortable side effects of abdominal distension.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-In-Part of U.S. patent applicationSer. No. 16/362,660, filed Mar. 24, 2019, which is a Continuation ofU.S. patent application Ser. No. 15/688,877, filed Aug. 29, 2017, whichis a Divisional application of U.S. patent application Ser. No.15/138,594, filed Apr. 26, 2016, now U.S. Pat. No. 9,775,865, and claimsthe benefit of U.S. Provisional Application No. 62/208,995, filed Aug.24, 2015 and U.S. Provisional Application No. 62/289,944, filed Feb. 2,2016, all of which are incorporated herein by reference in theirentirety.

BACKGROUND OF THE INVENTION Technical Field

The present invention relates to the field of gastroenterologicalsystems, and more particularly, to large intestine contents and acousticcharacterization.

Discussion of Related Art

Colonoscopy procedures, carried out routinely on a large number ofpatients, require a prior cleansing of the large intestine, which may becarried out by various means.

SUMMARY OF THE INVENTION

The following summary does not necessarily identify key elements norlimit the scope of the invention, but merely serves as an introductionto the following description.

One embodiment of the present invention provides a system comprising: awater delivery unit comprising a controllable water supply, configuredto introduce water controllably into the patient's large intestine, adrainage configured to drain, by gravity, the introduced water withcontents of the patient's large intestine, wherein the drainagecomprises a drainage pipe and at least one sensor configured tocontinuously measure an amount of drained water drained by the drainagepipe, and a controller configured to control the water introduction withrespect to the measured amount of drained water, keeping an amount ofwater retained in the patient below a specified water retentionthreshold to limit abdominal distension and alleviate uncomfortable sideeffects related to it.

One embodiment of the present invention provides a method comprising:introducing water controllably into a patient's large intestine,draining by gravity the introduced water with contents of the patient'slarge intestine, measuring, continuously, an amount of the drainedwater, and controlling the water introduction with respect to themeasured amount of drained water, keeping an amount of water retained inthe patient below a specified water retention threshold to limitabdominal distension and alleviate uncomfortable side effects related toit.

These, additional, and/or other aspects and/or advantages of embodimentsthe present invention are set forth in the detailed description whichfollows; possibly inferable from the detailed description; and/orlearnable by practice of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of embodiments of the invention and to showhow the same may be carried into effect, reference will now be made,purely by way of example, to the accompanying drawings in which likenumerals designate corresponding elements or sections throughout.

In the accompanying drawings:

FIGS. 1A-1E are high-level schematic illustrations of a large bowelcleansing systems, according to some embodiments of the invention.

FIGS. 2A-2C are high-level schematic illustrations of a system,according to some embodiments of the invention.

FIGS. 3A-3D are high-level schematic flowcharts and illustrations ofmethods of deriving large intestine characteristics from acousticsignals, according to some embodiments of the invention.

FIGS. 4A and 4B are high-level flowcharts illustrating methods,according to some embodiments of the invention.

DETAILED DESCRIPTION

Prior to the detailed description being set forth, it may be helpful toset forth definitions of certain terms that will be used hereinafter.

The term “large intestine characteristics” as used in this applicationrefers to any feature that may be used to relate to the large intestine,such as its shape, length, diameter, position in the abdomen, anyrelated structures, such as appendages and pouches, the large intestinemay have, any changes in the form of the large intestine, features ofthe large intestine wall and its muscular activity, as well as featuresthat are related to measured acoustic signals, such as signal levels,signal frequencies, temporal and/or spatial distribution of the signalsand relation of the signals to any external or internal event such asintroduction of water into the large intestine and the cleansing of thelarge intestine. The term “large bowel” is used interchangeably with theterm “large intestine”.

The term “microbiota transplant” or “MT” as used in this applicationrefers to any introduced sample of intestinal bacteria such as fecaltransplants (fecal microbiota transplants—FMT) from autologous (self)sources or from donors, as well as any probiotic infusions.

In the following description, various aspects of the present inventionare described. For purposes of explanation, specific configurations anddetails are set forth in order to provide a thorough understanding ofthe present invention. However, it will also be apparent to one skilledin the art that the present invention may be practiced without thespecific details presented herein. Furthermore, well known features mayhave been omitted or simplified in order not to obscure the presentinvention. With specific reference to the drawings, it is stressed thatthe particulars shown are by way of example and for purposes ofillustrative discussion of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

Before at least one embodiment of the invention is explained in detail,it is to be understood that the invention is not limited in itsapplication to the details of construction and the arrangement of thecomponents set forth in the following description or illustrated in thedrawings. The invention is applicable to other embodiments that may bepracticed or carried out in various ways as well as to combinations ofthe disclosed embodiments. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Unless specifically stated otherwise, as apparent from the followingdiscussions, it is appreciated that throughout the specificationdiscussions utilizing terms such as “processing”, “computing”,“calculating”, “determining”, “enhancing” or the like, refer to theaction and/or processes of a computer or computing system, or similarelectronic computing device, that manipulates and/or transforms datarepresented as physical, such as electronic, quantities within thecomputing system's registers and/or memories into other data similarlyrepresented as physical quantities within the computing system'smemories, registers or other such information storage, transmission ordisplay devices. Any of the disclosed modules or units may be at leastpartially implemented by a computer processor.

Systems, kits and methods are provided, which analyze the largeintestine content and may utilize acoustic signals detected duringdelivery of water into the large intestine and drained large intestinecontents to derive large intestine characteristics. Systems may includea water delivery unit including a water supply and a nozzle connectedthereto, configured to introduce water controllably into a patient'slarge intestine, and an analysis unit that provides information aboutthe drained contents using optical examination or biological assays. Theinformation may be related to acoustic analysis of signals from acousticsensors that are attachable to a patient's abdomen. A variety of sensorconfigurations, positioning options, analysis strategies and largeintestine characteristics are presented.

Advantageously, as the gut microbiome is increasingly reported to relateto a variety of medical conditions (e.g., risk for cancer, inflammatorybowel disease (IBD), obesity, nonalcoholic fatty liver disease, arterialcondition, allergies and asthma, “reset” dysbiosis, such as caused bydietary changes, antibiotics, apnea, therapies, diseases, jetlag etc.),the ability to diagnose and transplant the microbiome is expected toprovide substantial benefits in many fields of medicine.

In certain embodiments, the systems, kits and methods may be integratedwithin a system or a procedure of large intestine cleansing prior tocolonoscopy, to provide additional information in form of the largeintestine characteristics to the practitioner of the upcomingcolonoscopy procedure.

Moreover, systems and methods are provided to limit abdominal distensionand limit and/or alleviate uncomfortable side effects related to it—inpatients treated in hydrocolonic preparation units. Systems may comprisea water delivery unit comprising a controllable water supply, configuredto introduce water controllably into the patient's large intestine, adrainage configured to drain, by gravity, the introduced water withcontents of the patient's large intestine and a controller. The drainagecomprises a drainage pipe and sensor(s) such as camera(s) configured tocontinuously measure the amount of drained water drained by the drainagepipe. The controller is configured to control the water introductionwith respect to the measured amount of drained water, keeping an amountof water retained in the patient below a specified water retentionthreshold to reduce uncomfortable side effects of abdominal distension.

It is noted that hydrocolonic preparation units that cleanse thepatient's large intestine generally cause abdominal distension in thesense that the water introduction unfolds the normally collapsedintestine to a certain extent. In various embodiments, disclosed systemsand methods provide control over the extent of distension that limitsthe abdominal distension to alleviate, limit or even avoid uncomfortableside effects of abdominal distension. As the extent of uncomfortableside effects is both patient specific and process-specific, disclosedembodiments provide ways to control the cleansing process with respectto limit or reduce side effects in relation to predefined thresholdsand/or patient indications during the treatment.

FIGS. 1A-1E are high-level schematic illustrations of a large bowel(large intestine) cleansing systems 100, according to some embodimentsof the invention. FIG. 1A illustrates schematically a part of system 100with a corresponding block diagram, FIGS. 1B and 1C illustrateschematically perspective views of systems 100, with and without thetreated patient, respectively, FIG. 1D illustrates schematically aprocessor in system 100 and FIG. 1E illustrated schematically largeintestine cleansing system 100. Systems 100 are used with a hydrocolonicpreparation unit 80 that is designed ergonomically to receive thepatient in a comfortable posture and apply large intestine cleansingprocedures to the patient.

Systems 100 comprise a water delivery unit 130 comprising a controllablewater supply 131, configured to introduce water (132) controllably intothe patient's large intestine, a drainage 151 configured to drain, bygravity, the introduced water with contents of the patient's largeintestine (139). Drainage 151 typically comprises a drainage pipe 138within unit 80 that removes the gravity-drained contents 139 and atleast one sensor 161 configured to continuously measure an amount ofdrained water drained by drainage pipe 138. For example, drainage pipe138 may be connected to a draining basin of unit 80 and drain theaccumulating water and drained content therefrom, by gravity. It isnoted that gravity-drained contents 139 includes mostly water that wasintroduced and then drained form the patient's large intestine, as wellas an amount of contents that originated in the patient's largeintestine and is rinsed and drained by the introduced water. In certainembodiments, a pipe 134A may be configured to deliver water from anexternal pressurized source, such as a faucet, to the top of waterdelivery unit 130 (see, e.g., FIG. 1C, and FIG. 1B illustratingschematically water supply 131 with a gauge 136) from which water can beintroduced (132, via pipe 134) by gravity into the patient's largeintestine, and then drained (139, via pipe 138) from the patient bygravity as well.

Systems 100 further comprise a controller 141 (e.g., as part of acontrol unit 140, see below, and/or as part of water delivery unit 130)that is configured to control water introduction 132 (via pipe 134) withrespect to the measured amount of drained water 139, keeping an amountof water retained in the patient below a specified water retentionthreshold to limit abdominal distension and reduce uncomfortable sideeffects thereof. It is noted that abdominal distension, resulting fromexcessive accumulation of water during the cleansing procedure, may beinconvenient to the patient to a degree that can hinder the cleansingprocedure. Systems 100 and controller 141 may be configured to limitabdominal distension and reduce uncomfortable side effects thereof byavoiding excessive introduction of water into the patient's largeintestine, in respect to the amount of water that was previouslyintroduced into the large intestine and to the amount of water that wasalready drained therefrom. In particular, systems 100 may be configuredto monitor the amount of liquid (denoted R(t)) retained in the patient'scolon and to control the flow of water to the colon in such a way as tosteer away from, e.g., the trigger point of nausea and uneasiness due toabdominal distension, where the process needs to be stopped to allowrecovery of the patient.

In various embodiments, the specified water retention threshold may bedefined in different ways, such as relying on typical and/or patientspecific values or indications. Typical distended bowel (largeintestine) volumes are between 0.7 liter and 4.4 liter, averaging 2.1liter. Typical lengths of large intestines range between 118 cm and 285cm, averaging 197 cm. The specified water retention threshold foravoiding uneasiness due to abdominal distention may be determined as avalue that is lower than the average of 2.1 liter, e.g. 2 liter, 1.8liter, 1.5 liter or other values. Thresholds for limiting abdominaldistension and reducing the related side effects may be set as aspecified percentage of the typical and/or patient-specific distendedbowel volume—e.g., any of 50%, 25-50%, 50-75%, 10-30% or any otherintermediate values or ranges. In certain embodiments, patientindications of uneasiness may be used to calibrate the threshold or thepercentage of the estimated patient's bowel volume, e.g., lowerthresholds may be set for sensitive patients while higher threshold maybe set for less sensitive patients, in either case possibly in relationto estimated physical dimensions of the patient's large intestine. Forexample, the patient may be asked to mark once (e.g., by an appropriate“event” button) when uneasiness starts, and the marked value of waterretention may be used as a reference for defining the threshold duringthe procedure for this patient.

In certain embodiments, variability among patients may be taken intoaccount, by correlating the specified water retention threshold withvarious measures of the patient such as height, weight, circumference ofthe abdomen, body mass index etc. Typically, thresholds may be largerfor larger patients. In certain embodiments, an estimation of initialbowel contents may be taken into account, lowering the threshold at thestart of the cleansing procedure. The estimation may be received fromthe patient, or be derived from initial drained contents during thecleansing procedure (e.g., the threshold may be raised after initialcleansing). In certain embodiments, the specified water retentionthreshold may be determined individually, e.g., following previousimaging data of the large intestine. In certain embodiments, thespecified water retention threshold may be determined individually,e.g., by patient indication of initial discomfort that may be used toset the specified water retention threshold below the amount of retainedwater at the time of the patient indication. Accordingly, the specifiedwater retention threshold may be adjusted according to feedback from thepatient.

Limiting abdominal distention and reducing uncomfortable side effectsthereof may be carried out in various ways. For example, controller 141may be adjusted manually 142, e.g., by a supervising personnel such as anurse, via a console 144, and/or controller 141 may be associated with aprocessor 143, such as a computing device 143 disclosed in FIG. 1Dbelow. Manual adjustment 142 and/or control by computing device 143 maybe carried out with respect to patient feedback, e.g., adjustments ofthe specified water retention threshold may be made in case the patientindicates initial uneasiness or other indication of commencing symptomsof abdominal distension.

In certain embodiments, measurements of sensor(s) 161 may be transferredto controller 141 per wire and/or via a wireless communication link 99.When associated with processor 143, controller 141 and/or processor 143may be configured to calculate the amount of water retained in thepatient as R(t)=I(t)−O(t), with I(t) denoting an amount of theintroduced water at any given time t and O(t) denoting an amount of thedrained water at any given time t. The continuous estimation of theamount of retained water may be used to provide a risk assessment forabdominal distension and enable to avoid reaching that state.

The amount I(t) of introduced water 132 may be integrated by controller141 and/or be displayed or visually estimated using gauge 136 (see FIG.1B), e.g., by the personnel operating system 100 and/or electronically.The amount O(t) of drained water 139 may be integrated by processor 143and/or controller 141 as explained below, and/or be displayed orvisually estimated using a window 152 (e.g., above pipe 138, possiblywith illumination 164 to improve visibility, see, e.g., FIG. 1C) and amirror 153 configured to enable the estimation of the amount andcharacteristics of drained water by the personnel operating system 100(and see FIG. 1E below).

Processor 143 may be further configured to estimate O(t) by integratingover time a liquid height h(t) in drainage pipe 138. For example,sensor(s) 161 may comprise one or more camera(s) 161 having a field ofview (FoV) covering a part of transparent drainage pipe 138 andconfigured to image that part externally, to determine the amount ofdrained water flowing by in pipe 138. A background 163 may be set in theFoV behind transparent pipe 138, to provide contrast for camera(s) 161.In a non-limiting example, sensor(s) 161 may comprise one or more videocamera(s) 161 that records transparent pipe 138 against a whitebackground 163 and associated with transmitter 162 configured tocommunicate the video stream to processor 143. In certain embodiments,illumination source 164 (illustrated schematically in FIG. 1C) may beused to enhance visibility and/or improve measurements by sensor(s) 161.In certain embodiments, sensor(s) 161 may be directly associated withprocessor 143 configured to pre-process the sensor measurements andderive data pertaining to the amount of drained water, which may then betransmitted to processor 143 associated with controller 141 and/ordirectly to controller 141. For example, sensor measurements (e.g.,direct measurements, images and/or video streams) may be processed tomeasure over time a liquid height h(t) (indicated schematically) indrainage pipe 138.

In certain embodiments, drained contents 139 may be assumed to includeonly water delivered by water delivery unit 130, ignoring added largeintestine content for the purpose of monitoring the amount of liquid(R(t)). Such assumption is reasonable as the amount of introduced wateris typically much larger than the amount of large intestine contentsremoved in the cleansing process. In certain embodiments, the amount oflarge intestine contents added to drained water to yield drainedcontents (O(t)) may be estimated in various ways, such as a fixedestimation or an estimation from the measurements by sensor(s) 161.Denoting drained contents O(t)=W(t)+C(t), with W(t) denoting drainedwater which was previously introduced into the large intestine and C(t)denoting contents of the large intestine that was drained with the waterfor cleansing the large intestine, both as expressed time-dependentamounts−various embodiments may comprise any of the following: (i)ignoring C(t), assuming O(t)=W(t); (ii) assuming a fixed ortime-dependent estimation C′(t) for C(t), assuming O(t)=W(t)+C′(t);(iii) estimating C(t) from the sensor measurements, for example inrelation to the level of cleanliness of drained contents 139 as measuredby the optical density or any other measure of the relative amount ofmaterial originating from the large intestine in drained contents 139.In certain embodiments, illumination source 164 may be configured toenhance the measurement of W(t) and/or C(t), e.g., by using one or moreappropriate wavelengths for the measurements, with sensor(s) 161 andprocessor(s) 143 possibly being configured to distinguish introducedwater from contents of the large intestine that was drained with thewater, e.g., spectrally by comparing measurements at differentwavelengths.

In certain embodiments, sensor(s) 161 may be further configured toextract over time diagnostic parameters of drained contents 139 from themeasurements. For example, measured diagnostic parameters may comprisethe color and/or consistency of drained contents 139 over time,optionally relating the diagnostic parameters to the timing of drainageand correlating them with an estimated source location in the patient'slarge intestine, as disclosed below.

In certain embodiments, as disclosed below, water delivery unit 130 maybe further configured to modify a pressure of 132 introduced water,e.g., in relation to drained contents 139 and properties thereof, suchas its amount over time and/or the measured diagnostic parameters.Pressure modification may be used to enhance the cleaning process, thederived diagnostic parameters and/or the correlation to the location inthe large intestine, while disclosed monitoring of the amount of drainedwater may be used as disclosed, to limit abdominal distension andalleviate uncomfortable side effects related to it.

In various embodiments, as disclosed below (see, e.g., FIG. 1E), systems100 may further comprise an analysis module 160 configured to determinea large intestine cleanliness level according to drained contents 139 ofthe patient's large intestine and/or to derive large intestinecharacteristics by analyzing at least one portion of drained contents139, possible with the deriving being carried out using at least most ofdrained contents 139.

FIG. 1D is a high-level block diagram of exemplary computing device 143,which may be used with embodiments of the present invention. Computingdevice 143 may include a controller or processor 173 that may be orinclude, for example, one or more central processing unit processor(s)(CPU), one or more Graphics Processing Unit(s) (GPU or general purposeGPU-GPGPU), a chip or any suitable computing or computational device, anoperating system 171, a memory 172, a storage 175, input devices 176 andoutput devices 177. Any of system 100, processing unit 120, waterdelivery unit 130, control unit 140 and/or controller 141, processor143, optical inspection unit 150, analysis module 160 or other systemmodules may be or include a computer system as shown for example in FIG.1D.

Operating system 171 may be or may include any code segment designedand/or configured to perform tasks involving coordination, scheduling,arbitration, supervising, controlling or otherwise managing operation ofcomputing device 143, for example, scheduling execution of programs.Memory 172 may be or may include, for example, a Random Access Memory(RAM), a read only memory (ROM), a Dynamic RAM (DRAM), a SynchronousDRAM (SD-RAM), a double data rate (DDR) memory chip, a Flash memory, avolatile memory, a non-volatile memory, a cache memory, a buffer, ashort term memory unit, a long term memory unit, or other suitablememory units or storage units. Memory 172 may be or may include aplurality of, possibly different memory units. Memory 172 may store forexample, instructions to carry out a method (e.g., code 174), and/ordata such as user responses, interruptions, etc.

Executable code 174 may be any executable code, e.g., an application, aprogram, a process, task or script. Executable code 174 may be executedby controller 173 possibly under control of operating system 171. Forexample, executable code 174 may when executed cause the production orcompilation of computer code, or application execution such as VRexecution or inference, according to embodiments of the presentinvention. Executable code 174 may be code produced by methods describedherein. For the various modules and functions described herein, one ormore computing devices 143 or components of computing device 143 may beused. Devices that include components similar or different to thoseincluded in computing device 143 may be used, and may be connected to anetwork and used as a system. One or more processor(s) 173 may beconfigured to carry out embodiments of the present invention by forexample executing software or code.

Storage 175 may be or may include, for example, a hard disk drive, afloppy disk drive, a Compact Disk (CD) drive, a CD-Recordable (CD-R)drive, a universal serial bus (USB) device or other suitable removableand/or fixed storage unit. Data such as instructions, code, VR modeldata, parameters, etc. may be stored in a storage 175 and may be loadedfrom storage 175 into a memory 172 where it may be processed bycontroller 173. In some embodiments, some of the components shown inFIG. 1D may be omitted.

Input devices 176 may be or may include for example a mouse, a keyboard,a touch screen or pad or any suitable input device. It will berecognized that any suitable number of input devices may be operativelyconnected to computing device 143 as shown by block 176. Output devices177 may include one or more displays, speakers and/or any other suitableoutput devices. It will be recognized that any suitable number of outputdevices may be operatively connected to computing device 143 as shown byblock 177. Any applicable input/output (I/O) devices may be connected tocomputing device 143, for example, a wired or wireless network interfacecard (NIC), a modem, printer or facsimile machine, a universal serialbus (USB) device or external hard drive may be included in input devices176 and/or output devices 177.

Embodiments of the invention may include one or more article(s) (e.g.,memory 172 or storage 175) such as a computer or processornon-transitory readable medium, or a computer or processornon-transitory storage medium, such as for example a memory, a diskdrive, or a USB flash memory, encoding, including or storinginstructions, e.g., computer-executable instructions, which, whenexecuted by a processor or controller, carry out methods disclosedherein.

Aspects of the present invention are described above with reference toflowchart illustrations and/or portion diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each portion of the flowchartillustrations and/or portion diagrams, and combinations of portions inthe flowchart illustrations and/or portion diagrams, can be implementedby computer program instructions. These computer program instructionsmay be provided to a processor of a general-purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or portion diagram or portions thereof.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or portiondiagram or portions thereof.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/orportion diagram or portions thereof.

The aforementioned flowchart and diagrams illustrate the architecture,functionality, and operation of possible implementations of systems,methods and computer program products according to various embodimentsof the present invention. In this regard, each portion in the flowchartor portion diagrams may represent a module, segment, or portion of code,which comprises one or more executable instructions for implementing thespecified logical function(s). It should also be noted that, in somealternative implementations, the functions noted in the portion mayoccur out of the order noted in the figures. For example, two portionsshown in succession may, in fact, be executed substantiallyconcurrently, or the portions may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each portion of the portion diagrams and/or flowchart illustration,and combinations of portions in the portion diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

FIG. 1E is a high level schematic illustration of large bowel cleansingsystem 100, according to some embodiments of the invention. Embodimentsof large bowel cleansing system 100 may be integrated with embodimentsof kit 101 for acoustic sensing as described below.

System 100 may include water delivery unit 130 (also see FIG. 2A below)including water supply 131 and nozzle 135 connected thereto, configuredto introduce water controllably into the patient's large intestine,drainage 151 configured to drain, by gravity, the introduced water withcontents of the patient's large intestine (denoted by numeral 139), andanalysis module 160 configured to determine a large intestinecleanliness level according to drained contents 139 of the patient'slarge intestine. Analysis module 160 may be further configured to derivepatient diagnostics by analyzing drained contents 139 of the patient'slarge intestine. For example, the analyzing may be carried out using abiological assay of drained contents 139, such as an application ofcancer markers thereto. Advantageously, the analysis may be carried outusing at least most of drained contents 139 or all of drained contents139, thus providing a sample having a large volume that may enableefficient and sensitive diagnosis.

In certain embodiments, the drained large intestine's contents may beseparated after its original location in the large intestine, e.g.,contents of the left colon, the central colon and the right colon may beseparated from each other and be characterized independently(physically, optically, chemically and/or biologically). Specificsections of the large intestine may be separated from the rest of thelarge intestine's content, according to specified definitions that mayrelate to the patient's possible medical conditions. A sequence ofsections of the large intestine may be diagnosed independently, both inrespect to contents as well as acoustically. The acoustic measurementsmay be used as indicators for the splitting of the large intestine intosections and/or may provide additional data for the analysis of thelarge intestine's contents from each section. The spatial informationconcerning the contents of the large intestine may be utilize to providemore effective medical diagnosis, as certain conditions may belocation-specific, and isolating the contents from a specific section ofthe large intestine may provide more concentrated samples for analysisthan the whole bowel contents. The possibility provided by the system toregister the position of each portion of the contents opens up a newdimension in the ability to pinpoint the origins of various largeintestine medical conditions (it is known, for example, that certainconditions originate from very specific locations in the largeintestine, and that the microbiota may vary significantly along thelarge intestine).

In certain embodiments, drained contents 139 may flow via a transparentdrainage pipe 138 as part of drainage 151 and the analyzing may becarried out optically through transparent drainage pipe 138, e.g., asdisclosed above. For example, a light source (below window 152) may belocated next to the transparent drainage pipe and analysis module 160may employ optical analysis methods using camera(s) 161 and imageprocessing software, possibly as part of optical inspection unit 150(illustrated in FIG. 2A). It is noted that camera 161 may be the same asthe one used to estimate the amount of drained water 139 (see, e.g.,FIG. 1A above) or may be set in addition thereto, depending on thespatial configuration of system 100. Camera 161 may be used to recordeffluent 139 seen in viewing tube 138 for monitoring progress ofcleanliness of the bowel from a control center external to the roomwhere the patient is located, and an analytical tool in analysis module160 may be configured to perform analysis of pathological indicatorse.g., excretion of red blood, black stool, indicators of diverticula(such as corresponding pellets of stool). Image processing may becarried out locally or by a remote service and diagnosis of the imagesmay be carried out automatically (e.g., by the analytical tool),manually, e.g., by a local or remote expert or by a combination thereof.The analytical tool may comprise algorithms configured to generatecorresponding alerts once finding suggest any type of abnormality.

Analysis module 160 may be further configured to relate at least twoportions of the drained contents with at least two sections of the largeintestine. The relation may be carried out e.g., according to the timeof drainage of the portions, according to characteristics of the drainedcontent (e.g., consistence, shape, color, etc. related to diagnosedconditions in the large intestine sections), according to acousticmeasurements of the large intestine section and the drainage and/oraccording to modifications in the pressure of the introduced water anddrained contents, which may be related to positional information alongthe large intestine.

Analysis module 160 may be further configured to derive microbiomecharacteristics of the at least two sections of the large intestine byanalyzing the corresponding at least two portions of the drainedcontents. For example, a diversity, an abundance, and chemical and/orgenetic characteristics of the microbiome may be derived from analyzingdifferent portions of the contents. The microbiome characterization maybe used to reinstate the original microbiome after a treatment, or bemodified under spatial analysis of a present and a specified microbiome.In certain embodiments, the drained contents may be used to provide aFMT for transplantation after a treatment as an auto-FMT. Any type ofmicrobiotic infusion may be used as microbiota transplant (MT) toenhance or replace the characterized microbiome, at least on one sectionof the large intestine. Advantageously, system 100 enables use of mostor all of the drained contents for characterizing the microbiome of thepatient, thus providing an exhaustive and reliable analysis.

For example, the microbiotic diagnosis and transplant may be used todiagnose and treat Clostridium difficile (C. diff) infections. Thecombined treatment of cleansing the large intestine and transplanting aMT may be combined using system 100, thus becoming cleansing andtransplantation system 100. Moreover, system 100 may be used to providea healthy donor-based stool bank, which stores large intestine contentsfrom healthy subjects (being prepared from colonoscopy examinations bycleansing system 100) that may be used for research and treatment.Moreover, donors to the stool bank may utilize the stored probes formicrobiome rehabilitation after deterioration, thus treating “reset”dysbiosis, such as caused by dietary changes, antibiotics, apnea,therapies, diseases, jetlag, by autologous FMT. The whole stool samplingmay be used to overcome the inherent patchiness of the microbiome andpatchiness patterns may be analyzed using the accumulating contents frommany patients.

Certain embodiments comprise using system 100 to drain and to store aplurality of the drained contents' samples from a plurality of thepatients, in association with the derived microbiome characteristics ofthe drained contents samples. Moreover, system 100 may be utilized toestablish a stool bank for storing and providing drained contents'samples. Certain embodiments comprise a stool bank with the plurality ofdrained large intestine contents' samples from the plurality ofpatients, associated with derived microbiome characteristics of thedrained large intestine contents samples, wherein the drained largeintestine contents' samples are drained by gravity after controllablewater introduction into the patients' large intestines. The samples maybe used in different ways, e.g., for infusion (transplantation) ofcertain pre-screened stool samples and/or of related microbiomeinfusions; for administering of specific bacteria, probiotics, orantibiotics related to the derived microbiome characteristics; forinfusion (transplantation) of autologous samples; for prescribing foodadditives, food supplements, medications and/or therapies related to thederived microbiome characteristics. Any of the above may be related tospecific patients and/or to specific patient groups.

Returning to FIG. 1E, in certain embodiments, mirror 153 abovetransparent drainage pipe 138 may reflect drained contents 139 to acamera and an image processing unit, and/or to a staff person todetermine the consistency of drained contents 139, specific diagnosticappearances (e.g., color, objects etc.) and eventually the cleanlinesslevel of the patient's large intestine by noting the amount of drainedcontent 139 flowing through drainage 151. It is noted that mirror 153may also be used by the patient and/or by a staff member to simplify theprocess of inserting nozzle 135 into patient's anus 96. Alternatively orcomplementarily, a utensil 185 including two mirrors 153A, 153B mountedon a handle 186 may be configured to enable visualization of the nozzleinsertion by the patient and/or by the physician. Utensil 185 may bedesigned or be configurable to enable easy self-insertion of nozzle 135into anus 96 by the patient, or simplify the insertion procedure whencarried out by a physician or other medical personnel.

System 100 may include a support 180 configured to support the patient'slegs to help the patient maintain an appropriate posture during theprocedure. For example, support 180 may have two interconnected hooks180A, one for supporting each leg or knee. Hooks 180A may beinterconnected by any connecting member 180B such as a flexible or rigidstrap or bar, a band etc. Support 180 may be configured to anchor thelegs of the patient on hydrocolonic preparation system 100, allowing thelegs to fall sideways while supporting them against each other (theforce applied by each leg on respective hook 180A are balanced andmaintained by connecting member 180B) to maintain a required postureconveniently, as water flows through the nozzle into the rectum. Support180 may be configured to allow the patient to sit comfortably in therequired position for an extended period of time as may be required bythe procedure.

In certain embodiments, analysis module 160 may be further configured toderive large intestine characteristics by analyzing parameters ofdrained water and contents 139. For example, an exceptionally largeamount of contents 139 may signify a large volume of large intestine, orcontents 139 with specific features may be used to indicate specificlarge intestine features (e.g., small hard round clumps may signifylarge intestine diverticula). Certain large intestine characteristicsmay be corroborated by deriving them from both the acoustic signals andthe contents analysis.

In certain embodiments, system 100 may further include a MT unit 170configured to transplant a microbiota transplant (MT) such as a fecalmicrobiota transplant (FMT) into the patient's large intestine after apredetermined cleanliness level thereof is determined. MTtransplantation may be carried out e.g., via water supply, before orafter cleansing and/or colonoscopy.

In certain embodiments, water delivery unit 130 may be furtherconfigured to modify a pressure of introduced water 132 and analysismodule 160 may be further configured to measure a pressure of drainedwater and contents 139, and derive large intestine characteristics bycorrelating the measured drainage pressure with the pressure ofintroduced water according to a specified model. The reaction of thelarge intestine to different pressures may indicate certaincharacteristics thereof, such as peristaltic parameters of the largeintestine and possibly certain anomalies. Measuring the difference inpressure between the water flowing into the anus (132) and the effluentflowing out of the anus (139) may be used to provide new informationregarding the effectiveness of the peristaltic waves created by themuscles of the colon. Acoustic signals relating to the introduction ofpressurized water may also be analyzed to derive additional informationabout the large intestine, so that the analysis of the acoustic signalsand the analysis of the contents of the large intestine may be combinedsynergistically.

Certain embodiments may include any combination of acoustic signalsensing and large intestine content analysis. For example, system 100may include water delivery unit 130 including water supply 131 andnozzle 135 connected thereto, configured to introduce water controllablyinto the patient's large intestine, drainage 151 configured to drain, bygravity, the introduced water with contents of the patient's largeintestine, acoustic sensor(s) 110 that are attachable to the patient'sabdomen, and processing unit 120, possibly incorporating analysis unit160, configured to determine a large intestine cleanliness levelaccording to drained contents 139 of the patient's large intestine aswell as to derive large intestine characteristics by analyzing andcorrelating acoustic signals received from acoustic sensors 110, towhich processing unit 120 is connected, with parameters of the drainedwater and contents.

FIGS. 2A-2C are high level schematic illustrations of a system 100,according to some embodiments of the invention. It is noted thatelements of system 100 from FIGS. 1 and 2A may be combined to variousembodiments of system 100. System 100 may be used to calculate or deriveinformation about a patient's large intestine by processing acousticsignals received by sensors placed on the patient's abdomen. Theinformation may be provided to physician, e.g., as preparation forcolonoscopy procedures. It is noted that the illustrated elements of thepatient's digestive tract 90, namely stomach 91, small intestine 92,large intestine 93, sigmoid colon 94 (being the last part of largeintestine 93), rectum 95 and anus 96 are shown schematically, in anon-limiting manner. FIG. 2A schematically illustrates system 100 whileFIGS. 2B and 2C schematically illustrate sensor configurations,according to some embodiments of the invention. System 100 may beconfigured to cleanse the patient's large intestine, e.g., as apreparation for a colonoscopy procedure.

The inventors have found out that the acoustic signals, e.g., onesgenerated during the cleansing of the large intestine, may be used toderive significant information about the large intestine, such asindications whether the structure and position of the large intestineare normal or abnormal, simple or complex, and/or adequate or not forperforming colonoscopy (abnormalities and complexity may be of differentkinds); and various large intestine characteristics such as geometricparameters thereof and flow characteristics therethrough. The derivationof the large intestine characteristics may be carried outexperimentally, by relating measured acoustic signals to known largeintestine characteristics in a calibration process, utilizingtheoretical or empirical models describing flow properties through thelarge intestine and by comparing acoustic signals from different partsof the abdomen and/or from different measurement times to derivedifferences that are indicative of large intestine characteristics orprogress of the water flow and cleansing into the proximal largeintestine (closer to the cecum and distal to the anus). As a simpleexample, the measurement of flow noise may be used to indicate thelocation and general form of the large intestine. In another example,modifying water flow through the large intestine and correlation thereofwith the changing acoustic signals may be used to refine the measurementof geometrical parameters of the large intestine and furthermore provideinformation about flow patterns therethrough (e.g., indicate theresistance of the large intestine to flow, enable as evaluation ofintestine wall thickness, relate to the peristaltic movements of thelarge intestine etc.). Large intestine characteristics may be measuredspatially, relating to specific sections of the large intestine.

System 100 may include a water delivery unit 130 including a watersupply 131 (e.g., a container with a controlled outflow valve) and anozzle 135 connected thereto, configured to introduce water throughnozzle 135 controllably (as explained below) into a patient's largeintestine 93, a plurality of acoustic sensors 110 (e.g., microphones)that are attachable to a patient's abdomen, and a processing unit 120which is connected to acoustic sensors 110 and is configured tocalculate or derive large intestine characteristics by analyzingacoustic signals that are related to noise received from acousticsensors 110, the noises resulting from movements of water, large bowelcontent and/or air bubbles through the large intestine, that areinitiated through the water introduction. Sounds of water flowintroduced into the large intestine may allow diagnosing structuralfeatures of large intestine 93 such as its shape and layout, dimensionsof its various section, width along its length and presence of specificfeatures such as pouches (diverticula), redundant loops, irregulargeometrical and/or positional features etc.

In certain embodiments, acoustic sensors 110 may be configured tocommunicate with processing unit 120 over wires or wirelessly, thelatter via transmitters attached to acoustic sensors 110 which do nothave a galvanic connection to the patient's body.

System 100 may include a control unit 140 configured to control waterdelivery unit 130 according to instructions or control signals receivedfrom processing unit 120 which relate to the acoustic signals analysis.For example, water delivery may be stopped, increased, enhanced, madeperiodic or any parameters of water delivery may be modified in order,e.g., to verify or improve analysis initial findings.

Processing unit 120 may be configured to compare acoustic signalsemanating from the large intestine with acoustic signals emanating fromother regions, e.g., the small intestine, to identify and removebackground acoustic noise. For example, one or more sensors 110 may bepositioned away from large intestine 93 (see e.g., central sensor 110 inFIG. 2A or four central sensors in FIG. 2B) and their signals may beused as characterizing the background noise. Processing unit 120 mayreceive multiple channels from sensors 110, convert the analog audiosignals into digital signals (by analog to digital converter, ADC 121)and further process the digital signals.

Processing unit 120 may be configured to compare acoustic signals (fromlarge intestine noises) received before the water introduction withacoustic signals received after the water introduction and/or processingunit 120 may be configured to compare acoustic signals received beforethe introduced water reaches at least one specified region with acousticsignals received after the introduced water reaches the at least onespecified region. In certain embodiments, signals received from sensors110 positioned along large intestine 93 (see e.g., FIG. 2C and thecorresponding sensors in FIGS. 2A and 2B) and sampled sequentially totrack water reaching the corresponding large intestine sectionspositioned below sensors 110. The sequential sampling may includesampling sensors 110 according to the position along the largeintensity, sampling one or more sensors 110 sequentially over aspecified period of time (e.g., over the time it takes to fill and/orempty the large intestine) and/or any combination of these samplingapproaches. In certain embodiments, water delivery unit 130 may beconfigured to introduce air bubbles of different sizes into the largeintestine (e.g., air bubbles of different sizes maybe introducedsimultaneously or bubbles of uniform but selectable size may beintroduced at one or several times), and processing unit 120 may beconfigured to calculate or derive information from acoustic signalsemitted due to the bubble introduction and bubble behavior in the largeintestine. For example, bubble-induced noises may be used to improve thedelineation of the large intestine, to derive information about thediameter of the large intestine at different portions thereof and/or toindicate pressure levels that characterize different sections of thelarge intestine (varying the pressure of introduced water, which isdescribed below, may be applied to achieve this end together with theintroduction of bubbles). Processing unit 120 may be configured toutilize and/or analyze any type of water-flow and air-flow modulationsand the progress along the large intestine of flow noise resulting fromthe introduction. Sensors 110 may be placed accordingly along thenominal location of the large intestine, and/or at additional locationsfor reference and/or for detecting abnormalities or exceptional featuresin the large intestine, especially ones relating to the performance of asubsequent colonoscopy procedure (see FIGS. 3A-3D below for more detailson the acoustic signal analysis).

In certain embodiments, acoustic sensors 110 may be attached along anexpected position of the patient's large intestine (see e.g., FIG. 2C),additional sensors 110 may be attached at at least one location asidefrom or not at the expected position of the patient's large intestine(see e.g., FIGS. 2A and 2B) and/or acoustic sensors 110 may be attachedat an array covering the patient's abdomen (see e.g., FIG. 2B). Thepositioning of sensors 110 may be optimized over a large number ofpatients and water delivery schemes and/or may be personalized accordingto each patient's specific characteristics and possibly modified in viewof accumulating analysis results.

In certain embodiments, sensors 110 may be connected to a frame orframework 112 configured or adapted to an expected form of the patient'slarge intestine. Framework 112 may be stiff or flexible, and may allowaccommodation to the shape and dimensions of the patient's abdomen.Sensors 110 may be attached to the patient's abdomen by various meanssuch as suction, adhesion (e.g., stickers), structural conformity to thepatient's abdomen and/or by the configuration of framework 112 to yieldeffective transfer of acoustic waves from the patient's body to sensors110. In certain embodiments, framework 112 may be wearable, e.g.,sensors 110 may be incorporated in a vest as framework 112, configuredto facilitate correct positioning of sensors 110.

In certain embodiments, the water introduction may include at least onetime period of continuous water introduction and at least one period ofa pulsated or intermittent water introduction, and processing unit 120may be configured to analyze acoustic signals received during the atleast two periods.

In certain embodiments, the sensed acoustic signals and/or thecalculated or derived large intestine characteristics may be used toderive an alert or indication concerning a consequent colonoscopyprocedure and/or an indication of large intestine anomaly, exceptionalfeatures or adequacy for colonoscopy. The alert or indication may bedelivered as any type of output, such as a textual indication, a visualor an auditory signal and so forth, and by any medium (e.g., a display,a speaker, a medical record etc.). In certain embodiments, thecalculated or derived large intestine characteristics may include forexample: an indication of large intestine anomaly, a categorization ofthe patient's large intestine (e.g., into medically significantclasses), at least one geometric parameter of at least one region of thelarge intestine (e.g., length, width, position, wall thickness, etc.)and at least one parameter of water flow through the large intestine(such as throughput, speed of flow, regions which receive little or noflow, etc.).

Certain embodiments include a kit 101 (FIG. 2A) including acousticsensors 110 that are attachable to a patient's abdomen, and processingunit 120 connected to acoustic sensors 110 and configured to derivelarge intestine characteristics by analyzing acoustic signals receivedtherefrom, which are associated with water introduction to the patient'slarge intestine. The placing of sensors 110, configurations ofprocessing unit 120 and derived large intestine characteristics may besimilar to the one described above for system 100. Kit 101 may comprisethe parts of system 100 which handle the acoustic sensing andprocessing, such as acoustic sensors 110 and elements of processing unit120 and related units. Kit 101 may include placing instructions foracoustic sensors 110 and/or diagnostic flow(s) that relate processingresults with the large intestine characteristics and/or withcorresponding medical conditions.

In certain embodiments, system 100 may further include a drainage 151configured to drain, by gravity, introduced water with contents of thepatient's large intestine 139 and an analysis module 160 (which may bepart of, integrated with or include processing unit 120) that isconfigured to determine a large intestine cleanliness level according tothe drained contents of the patient's large intestine. Further detailswere provided above concerning FIGS. 1A-1E. Analysis module 160 maycomprise a separation unit 165 such as a mesh apparatus, configured toseparate contents of the large intestine such as feces from the water indrained contents 139.

System 100 may be configured to cleanse the patient's large intestine,e.g., as a preparation for a colonoscopy procedure. Water delivery unit130 may be further configured to introduce at least one additive 133with introduced water 132. Additive(s) 133 selected to enhance cleansingof the patient's large intestine. For example, at least one additive 133may include biological detergents that can be shown to be acceptable foruse in large intestine cleansing procedures.

Analysis of drained material 139 may be carried out, for exampleoptically, by an optical inspection unit 150 and/or using a biologicalassay, such as one including various markers, e.g., cancer markers.Processing unit 120 may be configured to determine existence of specificdiseases based on analyzing biological reactions of the contents of thepatients' large intestine to markers for such diseases. It is emphasizedthat the analysis may be carried out with respect to most or all of thelarge bowel contents, thus providing significant diagnostic advantagesover prior art diagnosis that is based on partial sampling of the largebowel content. The biological assay may be carried out as part of system100 or at least partially by external labs. The biological assay may becarried out in real-time, or at least partially a certain period afterthe contents has been drained.

Processing unit 120 and/or control unit 140 and/or analysis module 160may be configured to carry out methods according to embodiments of thepresent invention by for example executing software or code (for examplestored in memory 125) and/or by including dedicated circuitry.

FIGS. 3A-3D are high level schematic flowcharts and illustrations ofmethods 242 of deriving large intestine characteristics from acousticsignals, according to some embodiments of the invention. Methods 242 maycommence with acquiring or obtaining the acoustic signals (stage 221),denoted by P(x_(i), t)−P for the signals, x_(i) for the respectivelocation of the i^(th) sensor 110 and t for the time from the beginningof the measurements, inputting or receiving a start time t₁ and an endtime t₂ (stage 222) and determining a noise pattern {tilde over (P)}(x,t₁, t₂) (stage 223, and see FIG. 3D below). Then, FIG. 3A exemplifies anoption of displaying {tilde over (P)}(x, t₁, t₂) (stage 226A) forfurther visual analysis or for deriving certain alerts or indicationsthat are based on the appearance of the noise pattern, and then enablingdetermining the noise pattern {tilde over (P)}(x, t₁, t₂) for anotherinterval (t₁, t₂) (stage 222A). Alternatively or complementarily, FIG.3B exemplifies an option of deriving a ridge of {tilde over (P)}(x, t₁,t₂) (stage 231), the ridge representing the line of the smallestgradient of {tilde over (P)}(x, t₁, t₂) (alternatively orcomplementarily, the ridge may represent a central line of the noisepattern that exhibits the highest noise values in a set of crosssections of the pattern), and then displaying the ridge of {tilde over(P)}(x, t₁, t₂) (stage 226B) for further visual analysis or for derivingcertain alerts or indications that are based on the appearance andlocation of the ridge and then enabling determining the ridge of thenoise pattern {tilde over (P)}(x, t₁, t₂) for another interval (t₁, t₂)(stage 231A). As illustrated in FIG. 3D, a noise pattern 113 may expandbeyond large intestine 93, depending on the sensitivity of sensors 110,their density and locations, the propagation of noise through thepatient's abdomen and possible pre-processing algorithms applied to thesensor data. FIG. 3D illustrates schematically noise pattern 113 ({tildeover (P)}) which is centered along large intestine 93 and exhibits acentral ridge, i.e., a substantially linear region exhibiting the lowestgradient (and optionally the highest noise level along the crosssection) of noise pattern 113. FIG. 3D further illustrates schematicallychanges in noise intensity along the ridge in graph 122 and the crosssection of the pattern's intensity, topping at the ridge, in graph 124.Clearly, the wider pattern 113 is, more refined algorithms are requiredin order to detect the ridge. Sensors 110, their positions and/or thesound processing algorithms may be adjusted to optimize the detection ofa clear ridge in pattern 113. FIG. 3C exemplifies another option, ofbuilding a source model around an initial skeleton, which is atwo-dimensional projection of the ridge (e.g., onto the plane of thelarge intestine), then constructing a tubular noise source model aroundthe skeleton and refining skeleton to yield the closest noise pattern{tilde over (P)}(x, t₁, t₂) that fits the measured noise map (stage233), deriving a skeleton (as estimation of the central line of thelarge intestine) of the refined noise source model (stage 235), i.e.,estimating the outline of the large intestine, and displaying theskeleton as an approximation to the location of the large intestine(stage 226C). The skeleton may then be determined for another interval(t₁, t₂) (stage 235A), and the subsequent skeletons may be used forrefinements until a final, most accurate skeleton is reached and usedfor display. In certain embodiments, the dimensions and layout of thelarge intestine may be approximated by estimating the distribution ofwater flow noise sources in the abdomen by means of estimating theskeleton and dimensions of the noise source model that gives rise to themeasured and interpolated noise map. Comparisons of the noise sourcemodel at different times, or of developing noise source models over time(progress of water flow in the large bowel over time), or of differentnoise sources (with or without bubbles) or with and without water floware possibly based on the schemes illustrated in FIGS. 3A-3C. Using thenoise source model may improve the derivation of the location of thelarge intestine by taking into account models for noise propagationwithin the patient's abdomen, thus removing some of the spatialambiguity in the acoustic signals depicted by sensors 110.

FIGS. 4A and 4B are high-level flowcharts illustrating methods 200,according to some embodiments of the invention. Method 200 may becarried out using system 100, kit 101 and/or equivalent devices, orother equipment. Other operations or steps may be included. Method 200may be at least partially implemented by at least one computerprocessor. Certain embodiments comprise computer program productscomprising a computer readable storage medium having computer readableprogram embodied therewith and configured to carry out of the relevantstages of method 200, e.g., by processor 143. Method 200 may comprisethe following stages, from either or both FIGS. 4A and 4B, irrespectiveof their order.

As illustrated in FIG. 4A, method 200 may comprise introducing watercontrollably into a patient's large intestine (stage 210), draining, bygravity, the introduced water with contents of the patient's largeintestine, i.e., with the large bowel contents (stage 220), relating atleast two portions of the drained contents with at least two sections ofthe large intestine (stage 222) and deriving microbiome characteristicsof the at least two sections of the large intestine by analyzing thecorresponding at least two portions of the drained contents (stage 224).Method 200 may further comprise selecting a microbiota transplant (MT)such as a fecal microbiota transplant (FMT) or a microbiotic transfusionaccording to the derived microbiome characteristics of the at least twosections of the large intestine (stage 226) and transplanting the MT,possibly into a specified location related to the characterizedsection(s) of the large intestine (stage 228). The MT may comprise anautologous FMT, e.g., extracted prior to a treatment and transplantedafter the treatment, or any donor FMT or artificial microbiota.

Method 200 may comprise introducing water controllably into a patient'slarge intestine (stage 210), sensing acoustic signals at a patient'sabdomen (stage 240) and deriving large intestine characteristics byanalyzing the sensed acoustic signals associated with the waterintroduction (stage 242). In certain embodiments, method 200 may furtherinclude introducing at least one additive with the water to enhancecleansing of the patient's large intestine (stage 212), for example,biological and/or bio-compatible detergents that can be shown to beacceptable for use for cleansing the large intestine.

Method 200 may further include identifying local maxima in the sensednoise and deriving an estimated mid-line, or ridge, therefrom (stage244). In certain embodiments, method 200 may include modelling noisegeneration in the large intestine and deriving model parameters from themeasured noise patterns (stage 246).

Method 200 may include controlling the water introduction according toresults of the acoustic signals analysis (stage 248), e.g., to improvesensor readings, analysis and/or derivation of large intestinecharacteristics.

Method 200 may include for example comparing acoustic signals that aresensed before and after the water introduction (stage 250), comparingacoustic signals from different locations on the patient's abdomen(stage 255), and comparing acoustic signals that are sensed before andafter the introduced water reaches at least specified one region (stage260).

Method 200 may include introducing the water continuously and/or in apulsated manner (stage 215) and/or introducing air bubbles of differentsizes into the intestine (stage 217). Method 200 may include supportingthe patient's legs to help the patient maintain an appropriate posture(stage 218), e.g., by a utensil that has two interconnected hooks, onefor supporting each leg or knee. Method 200 may further includecomparing acoustic signals sensed during continuous and/or pulsatedwater introduction and/or bubble introduction (stage 265).

Method 200 may further include deriving at least one of: an alertconcerning a consequent colonoscopy procedure, an indication of a largeintestine anomaly, a categorization of the patient's large intestine,geometric parameter(s) of region(s) of the large intestine andparameter(s) of water flow through the large intestine (stage 270).

In certain embodiments, method 200 may include introducing watercontrollably into a patient's large intestine (stage 210), draining, bygravity, the introduced water with contents of the patient's largeintestine, i.e., with the large bowel contents (stage 220), anddetermining a large intestine cleanliness level according to the drainedcontents of the patient's large intestine (stage 290).

Method 200 may further include deriving patient diagnostics by analyzingthe drained contents of the patient's large intestine (stage 230). Forexample, the analyzing may be carried out optically, e.g., through atransparent drainage pipe. Additionally or alternatively, the analyzingmay be carried out using a biological assay (e.g., by application ofcancer markers) of the drained contents (stage 232). In certainembodiments, most or all of the drained contents may be used for theanalyzing (stage 235), improving thereby significantly the diagnosticpower of the analysis with respect to prior art methods which are basedon small samples of large bowel content.

Method 200 may further include deriving large intestine characteristicsby analyzing parameters of the drained water and contents (stage 300).Examples for deriving large intestine characteristics include geometricmeasures of the large intestine (e.g., volume, length, diameter),physiological measures and anomalies of the large intestine relating toparameters of the drained contents, and so forth. The derivations oflarge intestine characteristics by analyzing the sensed acoustic signalsassociated with the water introduction (stage 242) and by analyzingparameters of the drained water and contents (stage 230) may be combinedto verify findings and/or to derive compound large intestinecharacteristics. Moreover, the timing of the received acoustic signalsmay be correlated with the timing of content drainage to identify causesfor specific or generic types of acoustic noise received by the sensors.These analyses may be combined to derive or enhance the derivation oftemporal parameters of water and large bowel content flow through thelarge intestine.

In certain embodiments, method 200 may further include transplanting amicrobiota transplant (MT, the term is used as a generalized term toinclude fecal transplants and probiotic infusions) into the patient'slarge intestine after a predetermined cleanliness level thereof isdetermined (stage 310). MT/FMT transplantation may be carried out beforeor after colonoscopy, or as a separate procedure. The location for FMTtransplantation may be determined or evaluate according to the derivedlarge intestine characteristics, e.g., with reference to specificstructures, locations or abnormalities in the large intestine. Theefficiency of MT transplantation may be enhanced by selecting a locationwith predefined flow parameters which are conducive to successful MTtransplantation. MT transplantation may be carried out according to thederived patient diagnostics, e.g., upon detection of certain largeintestine infections, and responsive thereto.

Method 200 may further comprise storing drained contents' samples frommultiple patients, associated with their derived microbiomecharacteristics (stage 320) and establishing a stool bank for storingand providing drained contents' samples (stage 325), for auto- and/orallogenic (self and/or foreign) FMT transplantation.

In certain embodiments, method 200 may include modifying a pressure orflow of the introduced water (stage 216), measuring a pressure or flowof the drained water and contents (stage 280), and deriving largeintestine characteristics by correlating the measured drainage pressureor flow with the pressure or flow of introduced water according to aspecified model (stage 285). Exemplary large intestine characteristicsmay comprise characteristics of different sections in the largeintestine, relating e.g., to a left part, to a central part and to aright part of the large intestine. The spatial characterization of thelarge intestine's contents may be enhanced by the acoustic spatialcharacterization described above. Method 200 may comprise analyzing thelarge intestine's contents with respect to at least one portion of thecontents which correspond to a respective derived at least one sectionof the large intestine. The derivation of the specific section may becarried out physically, e.g. with respect to the volume of outflowingcontents, or acoustically, simultaneously with the acoustic sensingdescribed above.

As illustrated in FIG. 4B, method 200 may comprise introducing watercontrollably into a patient's large intestine (stage 210), draining bygravity the introduced water with contents of the patient's largeintestine (stage 220), measuring, continuously, an amount of the drainedwater (stage 330), and controlling the water introduction with respectto the measured amount of drained water, keeping an amount of waterretained in the patient below a specified water retention threshold tolimit abdominal distension and reduce uncomfortable side effects thereof(stage 340).

Method 200 may comprise continuously measuring of the amount of thedrained water 330 by capturing images of the drained water, opticallythrough a transparent drainage pipe (stage 332). Method 200 may furthercomprise calculating the amount of water retained in the patient asI(t)−O(t), with I(t) denoting an amount of the introduced water at anygiven time t and O(t) denoting an amount of the drained water at anygiven time t (stage 350). For example, method 200 may compriseestimating O(t) by integrating over time a liquid height h(t) in thedrainage pipe (stage 352). In certain embodiments, calculating 350 maybe carried out over changing water introduction parameters (stage 355).Method 200 may further comprise analyzing at least one portion of thedrained contents to derive diagnostic parameters of the drained contents(stage 230), a large intestine cleanliness level (stage 290) and/or thestructural and functional characteristics of the large intestine (stage300). Method 200 may further comprise any stage disclosed with relationto systems 100.

Aspects of the present invention are described above with reference toflowchart illustrations and/or portion diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each portion of the flowchartillustrations and/or portion diagrams, and combinations of portions inthe flowchart illustrations and/or portion diagrams, can be implementedby computer program instructions. These computer program instructionsmay be provided to a processor of a general purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or portion diagram portion or portions.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or portiondiagram portion or portions.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/orportion diagram portion or portions.

The aforementioned flowchart and diagrams illustrate the architecture,functionality, and operation of possible implementations of systems,methods and computer program products according to various embodimentsof the present invention. In this regard, each portion in the flowchartor portion diagrams may represent a module, segment, or portion of code,which comprises one or more executable instructions for implementing thespecified logical function(s). It should also be noted that, in somealternative implementations, the functions noted in the portion mayoccur out of the order noted in the figures. For example, two portionsshown in succession may, in fact, be executed substantiallyconcurrently, or the portions may sometimes be executed in the reverseorder, depending upon the functionality involved. It will also be notedthat each portion of the portion diagrams and/or flowchart illustration,and combinations of portions in the portion diagrams and/or flowchartillustration, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

In the above description, an embodiment is an example or implementationof the invention. The various appearances of “one embodiment”, “anembodiment”, “certain embodiments” or “some embodiments” do notnecessarily all refer to the same embodiments. Although various featuresof the invention may be described in the context of a single embodiment,the features may also be provided separately or in any suitablecombination. Conversely, although the invention may be described hereinin the context of separate embodiments for clarity, the invention mayalso be implemented in a single embodiment. Certain embodiments of theinvention may include features from different embodiments disclosedabove, and certain embodiments may incorporate elements from otherembodiments disclosed above. The disclosure of elements of the inventionin the context of a specific embodiment is not to be taken as limitingtheir use in the specific embodiment alone. Furthermore, it is to beunderstood that the invention can be carried out or practiced in variousways and that the invention can be implemented in certain embodimentsother than the ones outlined in the description above.

The invention is not limited to those diagrams or to the correspondingdescriptions. For example, flow need not move through each illustratedbox or state, or in exactly the same order as illustrated and described.Meanings of technical and scientific terms used herein are to becommonly understood as by one of ordinary skill in the art to which theinvention belongs, unless otherwise defined. While the invention hasbeen described with respect to a limited number of embodiments, theseshould not be construed as limitations on the scope of the invention,but rather as exemplifications of some of the preferred embodiments.Other possible variations, modifications, and applications are alsowithin the scope of the invention. Accordingly, the scope of theinvention should not be limited by what has thus far been described, butby the appended claims and their legal equivalents.

1. A system comprising: a water delivery unit comprising a controllablewater supply, configured to introduce water controllably into thepatient's large intestine, a drainage configured to drain, by gravity,the introduced water with contents of the patient's large intestine,wherein the drainage comprises a drainage pipe and at least one sensorconfigured to continuously measure an amount of drained water drained bythe drainage pipe, and a controller configured to control the waterintroduction with respect to the measured amount of drained water,keeping an amount of water retained in the patient below a specifiedwater retention threshold to limit abdominal distension and alleviateuncomfortable side effects related to it.
 2. The system of claim 1,wherein the controller is adjusted manually via a console.
 3. The systemof claim 1, further comprising a wireless communication link configuredto transfer measurements of the at least one sensor to the controller.4. The system of claim 1, wherein the controller is associated with aprocessor configured to calculate the amount of water retained in thepatient as I(t)−O(t), with I(t) denoting an amount of the introducedwater at any given time t and O(t) denoting an amount of the drainedwater at any given time t.
 5. The system of claim 4, wherein theprocessor is further configured to estimate O(t) by integrating overtime a liquid height h(t) in the drainage pipe.
 6. The system of claim1, wherein the at least one sensor comprises at least one camera.
 7. Thesystem of claim 6, wherein the drainage pipe is transparent and the atleast one camera is external to the drainage pipe and has a field ofview (FoV) covering a part thereof.
 8. The system of claim 6, furthercomprising a background set in the FoV behind the transparent pipe,wherein the background is configured to provide contrast for the atleast one camera.
 9. The system of claim 6, wherein the at least onecamera is configured to measure over time a liquid height h(t) in thedrainage pipe.
 10. The system of claim 1, wherein the at least onesensor is further configured to extract over time diagnostic parametersof the drained contents from the measurements.
 11. The system of claim1, wherein the water delivery unit is further configured to modify apressure of the introduced water.
 12. The system of claim 1, furthercomprising an analysis module configured to determine a large intestinecleanliness level according to the drained contents of the patient'slarge intestine.
 13. The system of claim 1, further comprising ananalysis module configured to derive large intestine characteristics byanalyzing at least one portion of the drained contents.
 14. The systemof claim 13, wherein the deriving is carried out using at least most ofthe drained contents.
 15. A method comprising: introducing watercontrollably into a patient's large intestine, draining by gravity theintroduced water with contents of the patient's large intestine,measuring, continuously, an amount of the drained water, and controllingthe water introduction with respect to the measured amount of drainedwater, keeping an amount of water retained in the patient below aspecified water retention threshold to limit abdominal distension andalleviate uncomfortable side effects related to it.
 16. The method ofclaim 15, wherein the continuous measuring of the amount of the drainedwater is carried out by capturing images of the drained water, opticallythrough a transparent drainage pipe.
 17. The method of claim 15, furthercomprising calculating the amount of water retained in the patient asI(t)−O(t), with I(t) denoting an amount of the introduced water at anygiven time t and O(t) denoting an amount of the drained water at anygiven time t.
 18. The method of claim 17, further comprising estimatingO(t) by integrating over time a liquid height h(t) in the drainage pipe.19. The method of claim 17, wherein the calculating is carried out overchanging water introduction parameters.
 20. The method of claim 15,further comprising analyzing at least one portion of the drainedcontents to derive at least one of: diagnostic parameters of the drainedcontents, a large intestine cleanliness level and structural andfunctional characteristics of the large intestine.